Pharmacokinetic and pharmacodynamic evaluation of sulbactam‐durlobactam in a critically ill patient on continuous venovenous hemofiltration infected with carbapenem‐resistant Acinetobacter baumannii‐calcoaceticus complex

Abstract Background Drug databases currently do not provide dosing guidance for sulbactam‐durlobactam in continuous renal replacement therapy. Herein, we present the first in vivo pharmacokinetic (PK) evaluation of sulbactam‐durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with carbapenem‐resistant Acinetobacter baumannii‐calcoaceticus complex (CRAB) bacteremia and ventilator‐associated bacterial pneumonia (VABP). Methods A 59‐year‐old critically ill patient (body mass index 60 kg/m 2 ) required CVVH and developed CRAB bacteremia secondary to VABP. Sulbactam‐durlobactam 2 g every 4 h infused over 3 h was initiated based on previous ex vivo data and the effluent rate of 6 L/h. The sulbactam‐durlobactam minimum inhibitory concentration (MIC) was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed. Steady‐state pre‐filter blood, post‐filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC). Results The sulbactam‐durlobactam MIC was 4/4 mcg/mL (susceptible). WGS revealed penicillin‐binding protein (PBP)‐1b and PBP‐3 mutations. The selected dose exceeded sulbactam and durlobactam PK/pharmacodynamic (PD) targets with 100% free time above MIC ( f T > MIC) and the ratio of area under the unbound concentration‐time curve to MIC ( f AUC/MIC) = 139, respectively. The SC for sulbactam and durlobactam was 0.68 and 0.67, respectively, and protein binding was 54% and 51%, respectively. Sulbactam‐durlobactam monotherapy resulted in initial microbiological clearance for CRAB bacteremia but recurred later in hospitalization 11 days after sulbactam‐durlobactam treatment. The patient was ultimately transitioned to comfort care. Conclusion Sulbactam‐durlobactam monotherapy dosed at 2 g every 4 h (3‐h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4/4 mcg/ml. Although sulbactam‐durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died.